Non- mutagenic photo chromic dye

ABSTRACT

A method of solubilizing a composition, such as an organic manufactured photochromic dye that is free of carcinogens, non-mutagenic, non-toxic to human skin in any concentration, and suitable for application to, and absorbable by, human skin. The photochromic dye is suitable to be applied directly to human skin, and which dye is configured to indicate exposure to UV rays. The composition is configured to change color upon exposure to UVA, UVB and/or UVC rays. The composition can be used with other compositions, such as sunscreen, and be applied to human skin prior to application of the sunscreen, or, formulated with the sunscreen such that when the active ingredients of the sunscreen diminish, the photochromic dye will change color to generate a visual indicator of this condition.

CLAIM OF PRIORITY

This application is a continuation-in-part (CIP) of U.S. patentapplication Ser. No. 15/293,054 filed Oct. 13, 2016 entitled Method,Composition for the Preparation and Cleaning of Photo Chromic DyesResulting in a Product Suitable for Use on Human Skin, which is acontinuation-in-part (CIP) of U.S. patent application Ser. No.15/145,410 filed May 3, 2016, issued as U.S. Pat. No. 9,545,374 B2,entitled Method, Composition for the Preparation and Cleaning of PhotoChromic Dyes Resulting in a Product Suitable for Use on Human Skin.

TECHNICAL FIELD

The present disclosure relates to a method of solubilizing an organicmanufactured photochromic dyes and inks, and a new manufacturing processthat removes known carcinogens and toxins from organic manufacturedphotochromic inks and dyes. This process creates cleaned, solubilizednon-mutagenic photochromic ink and dye materials suitable to be appliedto and absorbed by human skin without causing adverse reactions, andwhich meet U.S. Federal Drug Administration (FDA) requirements.

BACKGROUND

Over eighty percent of the population will experience some type ofreaction to their skin as a result of being exposed to Ultra Violet (UV)rays, such as UVA, UVB, and UVC rays. Such skin damage is photochemicalin nature and is directly associated with high energy, short wavelengthradiation. The end result is an undesirable biological change, such asinflammation and mutations to the DNA.

The use of photochromic dyes that illuminate with a wavelength between200 nm and 600 nm serve as indicators to the public alerting them oftheir exposure to Ultra Violet rays.

The current manufacturing processes of photochromic dyes result inresidual amounts of carcinogens remaining in, and on, these materials.By re-defining the manufacturing process, this disclosure provides aprocess to remove these carcinogens without altering chemical structureor function of the dyes.

These manufacturing processes are common throughout the industry forthose companies manufacturing photochromic dyes. These photochromic dyeswere not originally intended to be applied to human skin. Subsequently,there was no need to remove the affected carcinogens because the dyesand inks were used in other mediums (i.e. plastics, paper, t-shirts, andother novelty items).

SUMMARY

This disclosure provides a method of solubilizing a composition, such asan organic manufactured photochromic dye that is free of carcinogens,non-mutagenic, non-toxic to human skin in any concentration, andsuitable for application to human skin. The photochromic dye is suitableto be applied directly to and absorbed by human skin, and which dye isconfigured to indicate exposure to UV rays. The composition isconfigured to change color upon exposure to UVA, UVB and/or UVC rays.The composition can be used with other compositions, such as sunscreen,and be applied to human skin prior to application of the sunscreen, or,formulated with the sunscreen such that when the active ingredients ofthe sunscreen diminish, the chromic dye will change color to generate avisual indicator of this condition.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1A is an apparatus, and FIG. 1B is a conventional method forproducing a photochromic dye that includes carcinogens using theapparatus of FIG. 1A;

FIG. 2A is a diagram of a method for producing an organic manufacturednun-toxic photochromic dye without carcinogens, and which can bedirectly applied to human skin for detecting exposure to UVA, UVB, andUVC rays;

FIG. 2B is a diagram of a method for solubilizing the cleanedphotochromic dye;

FIG. 3 is a layout of a set-up for conducting an Ames test that iscommonly used to determine if a dye is tree of carcinogens andnon-mutagenic;

FIGS. 4A and 4B shows results from an Ames Out of Specification (OOS)test confirming the Ames test set-up of FIG. 3 is within Specification;and

FIGS. 5A and 5B is a chart detailing actual Ames test results fromcleaning a naphthopyran organic manufactured photochromic dye cleanedaccording to this disclosure, confirming the cleaned dye is free ofcarcinogens and is non-mutagenic.

DESCRIPTION OF EXAMPLE EMBODIMENTS

The following description of example embodiments provides informationthat enables a person skilled in the art to make and use the subjectmatter set forth in the appended claims, but may omit certain detailsalready well-known in the art. The following detailed description is,therefore, to be taken as illustrative and not limiting.

The example embodiments may also be described herein with reference tospatial relationships between various elements or to the spatialorientation of various elements depicted in the attached drawings. Ingeneral, such relationships or orientation assume a frame of referenceconsistent with or relative to a patient in a position to receivetreatment. However, as should be recognized by those skilled in the art,this frame of reference is merely a descriptive expedient rather than astrict prescription.

Conventional and toxic organic manufactured photochromic dyes thatinclude carcinogens are commercially available from numerous sources,such as Pittsburgh Paint and Glass of Pittsburgh, Pa. Illustrativeorganic manufactured photochromic dyes include siro oxazincs, which areblue dyes, and naphthopyrans that are yellow and red dyes. Because ofthe relative toxicity of these dyes when compared to other classes ofdyes, they are more suitable for medical and skin usage. These dyes alsohave the advantage that they fade rapidly. One preferred photochromicdye is fused naphthopyrans with an alkyl bridge between the pyran rings.

Other conventional toxic and carcinogenic dyes that can be cleanedaccording to this disclosure include azobenzenes, photo fulgides,photochromic fulgides and diarylenthene. Photochromic fulgides anddiarylenthene are fluorescing dyes.

Dyes are distinguished from pigments. A dye is a colored substance thathas an affinity to the substrate to which it is being applied and can beabsorbed by the substrate, and can be solubilized, such as in an ester.In contrast to a dye, a pigment is insoluble and has no affinity for thesubstrate. Dyes and pigments are distinct coloring substances. Dyes havesignificant advantages over pigments because dyes are absorbable in asubstrate including human skin, and thus last longer that a topicalpigment. In addition, pigments have a less vibrant color contrast, andare generally more expensive.

Conventional Cleaning Process for Photochromic Dyes

Referring to FIGS. 1A and 1B, there is shown a conventionalmanufacturing process at 10 for processing a chromic dye that is toxicand contains carcinogens. Toxic dyes are defined in this disclosure asdyes that are toxic to human cells in any concentration. Theconventional chromic dye is not suitable to be applied directly to humanskin, but rather to, mediums such as plastics, paper, t-shirts, andother novelty items.

At step 12, the-manufactured chromic dye is precipitated.

At step 14, the chromic dye is washed in a tank, also conventionallyreferred to as a reactor, in an equal portion of Carbon Tetra Chlorideand Chloroform.

At step 16, the chromic dye is re-crystallized and dried in a rotarydryer.

At step 18, the chromic dye crystals are washed in 100% methanol, driedand packed.

Cleaning Process for Chromic Dyes Suitable for Human Skin

Referring to FIG. 2A, there is shown one exemplary embodiment of amanufacturing process at 20 for producing a photochromic dye that isfree of carcinogens, non-toxic and suitable for application to humanskin, such as for use as a UVA, UVB and/or UVC indicator. Thephotochromic dye is configured to illuminate at a wavelength of between200 nm and 600 nm, although other wavelengths are possible.

At step 22, the step of washing the photochromic dye in Carbon TetraChloride and Chloroform previously described in step 14 is removedentirely from the manufacturing process. The photochromic dye is washedin a first tank a first time with an alcohol based solution, such as inequal portions, preferably a 100% methanol wash in one exemplaryembodiment. Ethanol Propanol can be used in another exemplaryembodiment. The photochromic dye may be washed at room temperature inone illustrative embodiment. The photochromic dye may also be washed at40 degrees Celsius to speed up the process in another illustrativeembodiment. The wash process may last for 4 hours in one illustrativeembodiment, but other longer and shorter times are acceptable. This stepremoves impurities that are harmful to human skin, such as toxins andcarcinogens.

At step 24, the photochromic dye is re-crystalized and dried, in oneillustrative embodiment, this may be done by vacuum filtering at roomtemperature. In another illustrative embodiment, the photochromic dyemay be cooled at 25 degrees Celsius, for 4 hours to speed up theprocess. In an optional step, the re-crystalized dried dye is mixed inequal portions with a 45% Tolune, 45% Heptane, and 10% Ethanol solution,and then vacuum cooled again, such as at 25 degrees Celsius, for 4 hoursto speed up the process. The wash process may last for 4 hours in oneillustrative embodiment, but other times are acceptable.

At step 26, the re-crystalized and dried photochromic dye is washed in asecond tank a second time in an alcohol based solution, such as in equalportions, preferably a 100% methanol wash in one exemplary embodiment,and Ethanol Propanol in another exemplary embodiment. The dye may bewashed at room temperature in one illustrative embodiment. In anotherillustrative embodiment, the dye may be washed at 40 degrees Celsius tospeed up the process. The wash process may last for 4 hours in oneillustrative embodiment, bin other shorter and longer times areacceptable. This additional wash is preferable, but not required if thewash of step 22 is sufficient to completely remove impurities that areharmful to human skin, such as toxins and carcinogens.

At step 28 the photochromic dye is re-crystalized and dried again. Inone illustrative embodiment, this may be done by vacuum filtering atroom temperature. In another illustrative embodiment, the dye may becooled at 25 degrees Celsius, for 4 hours to speed up the process.

At step 30, the re-crystallized and dried photochromic dye is thenwashed a first time in an acyclic aliphatic solution, preferably 100%heptanes. The dye may be washed at room temperature in one illustrativeembodiment. In another illustrative embodiment, the dye may be washed at40 degrees Celsius to speed up the process. The wash process may lastfor 4 hours in one illustrative embodiment although other longer andshorter times are acceptable. Acetone may be used in another exemplaryembodiment. This wash in 100% heptanes is effective to completely removeimpurities that are harmful to human skin, such as toxins andcarcinogens.

At step 32 the photochromic dye is re-crystalized and dried again. Inone illustrative embodiment, this may be done by vacuum filtering, suchas at room temperature. In another illustrative embodiment, this may bedone at 0 degrees Celsius, for 4 hours to speed up the process.

At step 34, the re-crystallized and dried photochromic dye is thenwashed a second time in an acyclic aliphatic solution, preferably 100%heptanes in one exemplary embodiment, and Acetone in another exemplaryembodiment. In one illustrative embodiment, the dye may be washed for 4hours at room temperature. In another illustrative embodiment, the dyemay be washed at 40 degrees Celsius to speed up the process.

At step 36, the photochromic dye is re-crystalized and dried. In oneillustrative embodiment this may be done by vacuum filtering at roomtemperature. In another embodiment, this may be done at 0 degreesCelsius, for 4 hours to speed up the process.

The resulting recrystallized non-toxic photochromic dye is then packagedfor sale and shipment as depicted in step 38. In one illustrativeembodiment, the dye may be vacuum packaged.

At step 40, upon receipt of the packaged non-toxic photochromic dye, andbefore formulation of the photochromic dye in a carrier, thephotochromic dye is washed and solubilized in an ester of 190-200 proofethanol to ensure that there is no trace of heptanes in the photochromicdye.

This process is safe, timely and cost effective.

In another exemplary embodiment, the photochromic dye can be washed onlyonce in an alcohol based solution, such as only once in methanol orEthanol Propanol, and only once in an acyclic aliphatic solution, suchas 100% heptanes or Acetone. However, performing each wash twice helpsensure the production of the non-toxic photochromic dye suitable forapplication to human skin. In another exemplary embodiment, thephotochromic dye may be washed more than once in an alcohol basedsolution, and more than twice in an acyclic aliphatic solution, such as100% heptanes.

Solubility

The cleaned photochromic dye operates as a UV indicator, and can beformulated into a cosmetic base and applied safely on human skin. Otherproducts, such as sunscreens, dermatology processes, anti-biotics,make-up and the like may be used with the cleaned photochromic dye.

The above described photochromic dye cleaning process 20 removes severalunwanted solvents that aided in the mixing/solubility of thephotochromic dye in many of cosmetic bases. Therefore, it isadvantageous to create a cosmetic lotion, anhydrous, solvent marker, geland hydro alcoholic solution to improve the solubility of the cleanedphotochromic dye for use in a cosmetic base.

Referring to FIG. 2B, there is shown a process 50 for creating acosmetic lotion, anhydrous, solvent marker, gel, and hydro alcoholicsolution configured to improve the solubility of the cleanedphotochromic dye as described above for use in a cosmetic base.

At step 52, a portion of the cleaned photochromic dye is placed in aclears. reactor.

At step 54, an appropriate amount of an ethanol is added into thereactor to create a mixture. For example, a preferred mixture may be 50%of cleaned photochromic dye and 50% of ethanol. A desired concentrationrange of the mixture is 45% to 55% of cleaned photochromic dye, althoughother concentrations may be suitable.

At step 56, the mixture of step 54 is heated in the reactor at avigorous speed to about 80 degrees Fahrenheit (F). The speed may bebetween 300 rotations per minute (RPM) and 800 RPMs until the cleanedphotochromic dye is totally dissolved in the ethanol. The mixture canhave a temperature of between 50 degrees F. and 100 degrees F.

At step 58, a water proofing, fast drying polymer or copolymer is addedto the mixture of step 56 in the reactor. The amount of the polymer orcopolymer may be 2-5% of the mixture after addition into the reactor.Suitable polymers include Styleze W-10 from ISP Technologies Inc. andGlossamer L-6600 from TRI K industries. The preferred polymer is StyezeW-10. This is a mixture of several materials. The next best preferredmaterial is the Glossamer L-6600.

The polymer or copolymer is advantageous to form a waterproof film thatcontains the dissolved cleaned photochromic dyes.

At step 60, a natural oil, such as a castor oil, is added to the mixtureof step 58 in the reactor, and the mixture is mixed until the polymer orcopolymer cross links. The amount of natural oil is 3-5% of the mixtureafter addition into the reactor. This is advantageous to 4% to 5%.

At step 62, the mixture of step 60 is then diluted to a volume with anester, such as an ethyl alcohol and/or C-12-15 benzoate alcohol ester.The mixture is then heated until all material has dissolved. Next,Dimethyl Isosorbide is added and mixed until the mixture is clear. Theamount of Dimethyl Isosorbide is 3% to 7% of the mixture. This isdesired to cross link the polymer or copolymer. This step completes thepreparation of a solubilized cleaned photochromic dye.

At step 64 the solubilized cleaned photochromic dye of step 62 is addedto a cosmetic base, such as a cosmetic lotion, anhydrous, solventmarker, gel, and hydro alcoholic solution. This creates a solubilizedmixture of a cosmetic base and cleaned photochromic dye that will easilybe absorbed into the skin of a mammal. This is because alcohol andDimethyl Isosorbide penetrate the skin.

Referring to FIG. 3, there is shown a conventional layout of a set-upfor performing an Ames test to determine if a dye has any carcinogensand if it is mutagenic. The Ames test is a widely employed method thatuses bacteria to test whether a given chemical can cause mutation in theDMA of the test organism. More formally, it is a biological assay toassay the mutagenic potential of a chemical compound. A positiveindicates that the chemical is a mutagenic compound and therefore mayact as a carcinogen because cancer is often linked to mutations.

The Ames test uses several strains of the bacterium Salmonellatyphimurium that carry mutations in genes involved in histidinesynthesis. These strains are auxotrophic mutants, i.e. they requirehistidine for growth, but cannot produce it. The method tests thecapability of the tested substance in creating mutations that result ina return to a “prototrophic” state, so that the ceils can grow on ahistidine-free medium.

The tester strains are specially constructed to detect either frameshiftstrains TA-1537 and TA-1538) or point (e.g. strain TA-1531) mutations inthe genes required to synthesize histidine, so that mutagens acting viadifferent mechanisms may be identified. Some compounds are quitespecific, causing reversions in just one or two strains. The testerstrains also carry mutations in the genes responsible forlipopolysaccharide synthesis, making the cell wail of the bacteria morepermeable, and in the excision, repair system to make the test moresensitive. Rat liver extract is optionally added to simulate the effectof metabolism, as some compounds, like benzo[α]pyrene, are not mutagenicthemselves but their metabolic products are.

The bacteria are spread on an agar plate with small amount of histidine.This small amount of histidine in the growth medium allows the bacteriato grow for an initial time and have the opportunity to mutate. When thehistidine is depleted only bacteria that have mutated to gain theability to produce its own histidine will survive. The plate isincubated for 48 hours. The mutagenicity of a substance is proportionalto the number of colonies observed.

AMES Test and Carcinogens

Mutagens identified via Ames test are also possible carcinogens, andearly studies by Ames showed that 90% of known carcinogens may beidentified via this test. Later studies however showed identification of50-70% of known carcinogens. The test was used to identify a number ofcompounds previously used in commercial products as potentialcarcinogens. Examples include tris (2,3-dibromopropyl) phosphate, whichwas used as a flame retardant in plastic arid textiles such aschildren's sleepwear, and furylfuramide which was used as anantibacterial additive in food in Japan in 1960s and 1970s.Furylfuramide in fact had previously passed animal test, but morevigorous tests after its identification in the Ames test showed it to becarcinogenic. Their positive tests resulted in those chemicals beingwithdrawn from use in consumer products.

One interesting result from the Ames test is that the dose responsecurve using varying concentrations of chemical is almost always linear,indicating that there is no threshold concentration for mutagenesis. Ittherefore suggests that, as with radiations, there may be no safethreshold for chemical mutagens or carcinogens. However, some proposedthat organisms can tolerate low level of mutagens due to protectivemechanisms such as DNA repair, and threshold may exist for certainchemical mutagens. Bruce Ames himself argued against lineardose-response extrapolation from the high dose used in carcinogenesistests in animal systems to the lower dose of chemicals normallyencountered in human exposure, as the results may be false positives dueto mitogenic response caused by the artificially high dose of chemicalsused in such tests. He also cautioned against the “hysteria over tinytraces of chemicals that may or may not cause cancer”, that “completelydrives out the major risks you should be aware of.”

The Ames test is often used as one of the initial screens for potentialdrugs to weed out possible carcinogens, and it is one of Use eight testsrequired under the Pesticide Act (USA) and one of six tests requiredunder the Toxic Substances Control Act (USA).

Referring to FIGS. 4A and 4B, an Out Of Specification (OOS) test inaccordance with Ames standards was performed on an Ames set-up accordingto FIG. 3, to qualify the set-up and validate the equipment used in theset-up as accurate and within Ames standard specifications. The datashown in FIG. 4A and verifies that the Ames set-up is withinSpecifications established by the Ames procedures.

Referring now to the chart in FIGS. 5A and 5B, there is shown detailedAmes test results of a cleaned naphthopyran photochromic dye accordingto the process of this disclosure using the qualified Ames set-up shownin FIG. 3. It can be seen that the Ames test results prove that thecleaned naphthopyran dye composition is non-mutagenic and free ofcarcinogens, and is non-toxic to human skin ceils in any concentration.

Additional Ames tests of all disclosed photochromic dyes identified inprevious paragraphs and cleaned according to the disclosed process showno residual carcinogens, that the cleaned photochromic dyes arenon-mutagenic, and the cleaned photochromic dyes are non-toxic to humanskin cells in any concentration.

The appended claims set forth novel and inventive aspects of the subjectmatter described above, but the claims may also encompass additionalsubject, matter not specifically recited in detail. For example, certainfeatures, elements, or aspects may be omitted from the claims if notnecessary to distinguish the novel and inventive features from what isalready known to a person having ordinary skill in the art. Features,elements, and aspects described herein may also be combined or replacedby alternative features serving the same, equivalent, or similar purposewithout departing from the scope of the invention defined by theappended claims.

1-18. (canceled)
 19. A composition of an organic manufacturedphotochromic dye that is free of carcinogens and is non-mutagenic,wherein the composition is made by a process that does not include anyknown carcinogens.
 20. The composition as specified in claim 19 whereinthe photochromic dye is selected from the group of: naphthopyrans withan alkyl bridge between pyran rings, siro oxazines, azobenzenes, photofulgides, photochromic fulgides, and diarylenthene.
 21. The compositionas specified in claim 19 wherein the photochromic dye is a naphthopyran.22. The composition as specified in claim 19 wherein the photochromicdye is a siro oxazine.
 23. The composition as specified in claim 19wherein the photochromic dye is solubilized in ethanol.
 24. Thecomposition as specified in claim 23 wherein the photochromic dye issolubilized in at least 190 proof ethanol.
 25. The composition asspecified in chum 19 wherein the photochromic dye is configured toilluminate at a wavelength between 200 nm and 600 nm.
 26. A compositionof an organic manufactured photochromic dye that is free of carcinogens,non-mutagenic, wherein the photochromic dye is a naphthopyransolubilized in ethanol, wherein the composition is made by a processthat does not include any known carcinogens.
 27. The composition asspecified in claim 26 wherein the naphthopyran photochromic dye issolubilized in at least 190 proof ethanol.
 28. The composition asspecified in claim 26 wherein the naphthopyran photochromic dye isconfigured to illuminate at a wavelength between 200 nm and 600 nm.